Antiviral agents, toxicity

Biomedical Uses. The molybdate ion is added to total parenteral nutrition protocols and appears to alleviate toxicity of some of the amino acid components in these preparations (see Mineral NUTRIENTS) (97). Molybdenum supplements have been shown to reduce iiitrosarnine-induced mammary carcinomas in rats (50). A number of studies have shown that certain heteropolymolybdates (98) and organometaUic molybdenum compounds (99) have antiviral, including anti-AIDS, and antitumor activity (see Antiviral agents Chemotherapeutics, anticancer). 

Before an antiviral agent becomes a drug, advanced toxicity testing, pharmacological combination, and drug-interaction studies are needed. The use of new cell-based assays that can predict mitochondrial toxicity, lactic acidosis, peripheral neuropathy, anemia, hypersensitivity, lipodystrophy, and other potential side effects can alleviate these issues (Stuyver et al. 2002). 

Considerable effort has gone into investigating compounds from tunicates over the past two decades. For unknown reasons these chemicals are often potent antiviral agents, whereas clinicians have few drugs active against viruses. Didemnin B was the first of these candidate compounds to be examined and initially it showed promise against a broad spectrum of viruses. After lengthy clinical trials, however, it was finally abandoned as too toxic for safe human use. 

Anthelmintic, antiprotozoal, anti-neoplastic, and antiviral agent Binds many proteins, i.e., cytokines. epidermal growth factor, and members of the FGF family inhibits dengue virus infec-tivity of host cells very long in vivo half-life, exhibits a wide range of toxic side effects 40-47... 

Idoxuridine (9.7) and trifluridine (9.8) are antiviral agents that are phosphorylated to their active form in virus-infected cells, and thus show specificity for two reasons their higher affinity for the viral enzyme, and the higher phosphorylase levels in viral-infected than in normal cells. Both compounds have been used locally on lesions of HSV-1 and HSV-2 (the latter of which causes genital herpes, now reaching epidemic proportions) with fair success. They are rather toxic if administered parenterally, as are all moderately selective antimetabolities. 

Viruses are obligate intracellular parasites their replication depends primarily on synthetic processes of the host cell. Consequently, to be effective, antiviral agents must either block viral entry into or exit from the cell or be active inside the host cell. As a corollary, nonselective inhibitors of virus replication may interfere with host cell function and produce toxicity. The search for chemicals that inhibit virus-specific functions is currently one of the most active areas of pharmacologic investigation. 

Which one of the following antiviral agents exhibits the greatest selective toxicity for the invading virus ... 

Viruses present a more difficult problem of chemotherapy than do higher organisms, e.g. bacteria, for they are intracellular parasites that use the metabolism of host cells. Highly selective toxicity is, therefore, harder to achieve. Identification of differences between viral and human metabolism has led to the development of effective antiviral agents, whose roles are increasingly well defined. 

Tubular cell toxicity This involves the cellular transport systems mentioned previously and is thus dose dependent to a degree. Examples of tubular cell toxins include aminoglycosides, calcineurin inhibitors, amphotericin, antiviral agents, cisplatin, methotrexate, contrast agents and cocaine. 

The ability to prevent viral infections is becoming an increasingly important part of clinical medicine. The interest in the development of new antiviral agents and new uses of these medications is driven in large part by the treatment of human immunodeficiency virus (HIV) and growth of the field of transplantation. Although most of the use of these antiviral agents is well-tolerated by patients, there are a variety of potential kidney toxicities that should be appreciated. The most important of these toxicities is acute kidney injury (AKI), which is the main focus of... 

Several selenium-substituted acyclouridine derivatives 115-120 were studied and their antiviral activity was evaluated in human peripheral blood mononuclear cells infected with HIV-1. Compounds 115 and 116 are the least and more effective compounds against HIV virus, respectively. Chemical modifications of the acyclic side chain produced compounds 121-124. Compound 124 is the most potent antiviral against HlV-1. The pharmacokinetics and toxicity studies on compound 124 clearly show that this compound can act as an effective antiviral agent at low concentrations without exhibiting toxicity. 

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